Separation of chemicals is widely and routinely performed in lots of industries and research labs. Liquid Chromatography (LC), and especially High Performance Liquid Chromatography (HPLC), is one of the most powerful and versatile separation techniques.
Although LC column is normally made of capillary tubes due to fluidics limitations, the miniaturization of the column can actually improve separation performance. As shown in FIG. 15 where same separation chemistry applies, separated peak width is independent of column ID, while peak heights are larger for smaller columns and/or smaller beads.
Conventional LC systems are also typically expensive and bulky. The separation columns, being of utmost importance in LC system, are also expensive and need replacements after a certain times of usage (typically about 100 times). Sample and solvent consumption cost is also very high.
A miniaturized LC system could be cheaper, faster, and exhibit minimized sample and solvent consumption. The need/market for miniaturized LC system is huge. However, comparing to the intense interests in miniaturized electrophoresis system on-a-chip, little is published about miniaturizing LC system onto a single chip. Harris et al., “Shrinking the LC Landscape”, Analytical Chemistry, pp. 64A-69A (February 2003), and de Mello, “On-chip chromatography: the last twenty years”, Lab on a Chip 2, 48n-54n (2002), both of which are incorporated by reference herein for all purposes, provide an overview of efforts in this area.
The main obstacles to miniaturization of LC systems are the lack of (1) a process to integrate various components of an LC system onto a monolithic chip; (2) high-pressure microfluidics needed for pumping liquid through densely-packed beads column; and (3) an approach to easily and reliably pack and seal chromatography supports (micro-beads) into the on-chip column.
From the above, it is seen that structures for performing liquid chromatography on small scales are highly desirable.